WO2014074920A1 - Procédé et appareil destinés à ajouter des tampons et d'autres substances à des cartouches médicales - Google Patents

Procédé et appareil destinés à ajouter des tampons et d'autres substances à des cartouches médicales Download PDF

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Publication number
WO2014074920A1
WO2014074920A1 PCT/US2013/069300 US2013069300W WO2014074920A1 WO 2014074920 A1 WO2014074920 A1 WO 2014074920A1 US 2013069300 W US2013069300 W US 2013069300W WO 2014074920 A1 WO2014074920 A1 WO 2014074920A1
Authority
WO
WIPO (PCT)
Prior art keywords
cartridge
anesthetic
medicament
buffer
plunger
Prior art date
Application number
PCT/US2013/069300
Other languages
English (en)
Inventor
Matthew STEPOVICH
Michael FALKEL
Mark Foley
Original Assignee
Onpharma, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Onpharma, Inc. filed Critical Onpharma, Inc.
Priority to JP2015541957A priority Critical patent/JP2015533619A/ja
Priority to EP13852986.2A priority patent/EP2916889A4/fr
Priority to KR1020157015002A priority patent/KR20150095651A/ko
Priority to AU2013342179A priority patent/AU2013342179A1/en
Priority to BR112015009466A priority patent/BR112015009466A2/pt
Priority to CA2888834A priority patent/CA2888834A1/fr
Priority to CN201380058386.5A priority patent/CN104918646A/zh
Priority to MX2015005807A priority patent/MX2015005807A/es
Publication of WO2014074920A1 publication Critical patent/WO2014074920A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2089—Containers or vials which are to be joined to each other in order to mix their contents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/06—Ampoules or carpules
    • A61J1/062—Carpules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
    • A61J1/2006—Piercing means
    • A61J1/201—Piercing means having one piercing end
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2096—Combination of a vial and a syringe for transferring or mixing their contents
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04C—ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; ROTARY-PISTON, OR OSCILLATING-PISTON, POSITIVE-DISPLACEMENT PUMPS
    • F04C2270/00—Control; Monitoring or safety arrangements
    • F04C2270/04—Force
    • F04C2270/042—Force radial
    • F04C2270/0421—Controlled or regulated

Definitions

  • the present invention relates generally to methods and apparatus for buffering medical solutions, such as anesthetics. More particularly, the present invention relates to methods for buffering and modifying medical solutions which are stored in small cartridges.
  • One particularly effective approach for combining a buffer or other material with an anesthetic or other medical solution utilizes a needle assembly including both a transfer needle and an exhaust needle.
  • One end of the transfer needle is inserted through a septum into the buffer cartridge and the other end is inserted through a septum into the anesthetic cartridge.
  • the exhaust needle is inserted through the same septum into the anesthetic cartridge and provides a path for removing excess anesthetic as the buffer is introduced into the cartridge, as described for example in commonly owned U.S. Pat. No. 8,162,917 and U.S. Publication No. 2011/0282316, the full disclosures of which are incorporated herein by reference.
  • Such systems result in a small amount of waste of the anesthetic and requires that the wasted anesthetic be managed.
  • local anesthetics are typically hypertonic as manufactured and delivered in dental anesthetic cartridges.
  • the anesthetics are also typically acidic, having a pH of from 3 to 5.5. Buffering anesthetics in cartridges toward physiologic pH using medical sodium bicarbonate solutions, as described above, represents one approach to address problems caused by the acidity of the anesthetic cartridges. The addition of sodium bicarbonate, however, increases the hypertonicity of the anesthetic solution.
  • the tonicity of a solution is often referenced as a measure of the solutes contained in a specified volume of liquid, where the solution's osmolality is typically expressed as milliosmoles of solute per liter (mOsm/L).
  • the tonicity of the solution is expressed as a measure of solutes contained in the weight of the sample, where the solution's osmolality is typically expressed as a milliosmoles of solute per kilogram (mOsm/kg).
  • Human physiologic osmolality is approximately 300 milliosmoles per liter (300 mOsm/L).
  • a liquid medicament cartridge comprises a hollow body having a first open end and a second open end.
  • the body will be cylindrical and comprised of glass or other material of the type conventionally used to store liquid medicaments, such as anesthetics and other parenteral solutions.
  • a needle- penetrable septum will be formed over the first open end, and a plunger will be spaced or displaced inwardly from the second open end, typically by a distance and a range from 0.5mm to 2 mm, typically being about 1mm for a dental anesthetic cartridge.
  • the hollow body will typically have a length and a range from 50mm to 75mm (typically being about 58mm for a dental anesthetic cartridge), an inner diameter in the range from 5mm to 10mm (typically being about 6.85mm for a dental anesthetic cartridge), and a volume in the range from 1ml to 5 ml (typically being about 2.1ml for a dental anesthetic cartridge).
  • a protective plug will be inserted into the second open end.
  • the protective plug will usually be displaceable as the plunger is advanced by the addition of liquid injected through the septum into an interior of the hollow body. In this way, even a very small displacement of the protective plug can alert the user that material has been added to the cartridge.
  • the plug by properly designing the plug, additional displacement can cause the plug to fall from or be easily grasped and removed from the hollow body, thus facilitating subsequent use of the cartridge. Finally, the presence of the plug in the cartridge can prevent use of the cartridge in a syringe system, reducing the risk that the cartridge would be used without first injecting the buffer or other material.
  • the protective plug may have a distal end which engages the plunger and a proximal end which covers the second opening to maintain sterility.
  • the proximal end will be enlarged or otherwise configured so that it cannot be pushed into the second open end to prevent premature inward displacement of the plunger.
  • the proximal end of the plug will be configured so that it is difficult to manually grasp when present over the second open end of the hollow body but easier to grasp when displaced proximally from the second open end.
  • a method for buffering anesthetic or other liquid medicament carried in a container comprises injecting or otherwise adding a buffer into an interior of the container to outwardly displace a plunger which in turn will eject a protective plug which covers the open end of the cartridge.
  • the protective plug preferably prevents contamination of the interior walls of the cartridge adjacent to the open end of the cartridge prior to ejection.
  • the protective plug will usually also prevent inward displacement of the plunger prior to removal of the plug, and in preferred examples the plug will be configured so that it cannot be pushed into the container.
  • a method for buffering a liquid anesthetic or other medicament having a target tonicity and a target pH comprises providing a volume of the liquid medicament in a sealed container having a septum at one end and a plunger at an opposite end.
  • the medicament within the container will include at least one solute and have an initial tonicity and an initial pH.
  • a volume of buffer is injected through the septum into the medicament.
  • An initial solute concentration and an initial pH of the liquid medicament are selected so that when the volume of buffer is combined with the medicament to achieve a target pH, the resulting buffered medicament will have both the target pH and the target tonicity.
  • the target tonicity is less than 500 mOsm/kg, typically being less than 400 mOsm/kg. In particularly preferred embodiments, the target tonicity will be substantially isotonic.
  • Anesthetics will usually have an original pH below 6 and the volume of buffer will be selected to raise the pH of the buffered anesthetic to a target pH of at least 7, preferably to at least 7.3.
  • the target tonicity will be 7.45.
  • the solute accompanying the anesthetic or other medical solution may comprise sodium chloride.
  • the medical solution may further include a vasoconstrictor, such as epinephrine or levonordefrine.
  • the buffer may comprise sodium bicarbonate, and the cartridge will typically be prepared at a central manufacturing facility, where the cartridges are then distributed to a plurality of local users, where the users typically add the buffer before delivering the anesthetic injection.
  • the users may be dentists or other practitioners who combine the buffer and anesthetic immediately prior to a procedure in order to produce buffered anesthetic for use in the procedure. In such cases, it will be desirable to introduce the buffer immediately prior to use, typically within two minutes of use.
  • the local anesthetics may be any one of a variety of anesthetics typically used in dentistry and elsewhere, such as amide local anesthetics and amine local anesthetics, with specific examples being lidocaine, articaine, mepivacaine, and the like.
  • the internal volumes of these cartridges may be in the range from 1.45 ml to 2.3 ml, the anesthetic volume may be in the range from 1.15 ml to 2.2 ml, and the buffer volume to be added may be in the range from 0.05 ml to 0.5 ml.
  • an anesthetic cartridge may instead be filled to a preselected volume less than its maximum, where the filled volume allows an additional volume of pH buffer to be added. While such additional volume will cause displacement of the plunger, such displacement will not result in the plunger being displaced to a point where the function of the cartridge is compromised.
  • such cartridges may also employ methods of maintaining the sterility of portions of the glass cartridge that would come into contact with the solution as the plunger is displaced outward.
  • the cartridge would include a mechanism that prevents the non-buffered cartridge from being loaded into the syringe until the pH buffering process has been completed, in order to prevent the injection of the contents of an unbuffered cartridge.
  • syringe can be loaded but the plunger cannot be displaced by the syringe.
  • an inventory of containers of local anesthetic solution having a lesser degree of osmotic pressure, or lower concentration of solutes, than the standard 2% local anesthetic solution currently available in the marketplace are provided.
  • the concentration of epinephrine in the pre-buffered cartridge would be adjusted so that after the addition of the pH buffer, the concentration of epinephrine would be at the standard for such anesthetics, for instance 1 :200,000, 1 : 100,000, or 1 :50,000.
  • Fig. 1 illustrates a prior art medical solution cartridge having buffer or other material transferred by a transfer needle.
  • FIG. 2 illustrates a plug according to the present invention suitable for insertion into an open plunger end of a medical solution cartridge in order to maintain the sterility of that end.
  • FIG. 3 illustrates the plug of Fig. 2 inserted into a medical solution cartridge of the type illustrated in Fig. 1.
  • Fig. 4 shows the effect of material transfer into the cartridge shown in Fig. 3 to displace the plug from the plunger end of the cartridge.
  • hypotonic local anesthetic solution that is intended to be buffered prior to use
  • a hypotonic local anesthetic solution would be manufactured to a known and precise osmolarity. This osmolality would be hypotonic, which means that it would have an osmolarity below that of human blood and tissues, which is approximately 300 mOsm/L (300 milliosmoles per liter).
  • the local anesthetic would be formulated to a sufficiently hypotonic level that with the addition of a desired amount of a known
  • the mechanism for adding the buffering solution to the anesthetic cartridge may include transferring buffering solution into the cartridge using a transfer needle, while an exhaust needle allows an equal amount of anesthetic solution to leave the cartridge.
  • the anesthetic cartridge would be manufactured having the plunger at a predetermine distance proximally toward the septum, such that with the addition of an intended amount of buffering solution, the plunger would move distally from the septum, but not past the open end of the glass cartridge.
  • a plunger that is placed 10mm proximal to the septum from the open end of a glass cartridge will be displaced approximately 10mm toward the open end of the cartridge with the addition of 0.35mL of solution.
  • the osmolarity of the solution would be such that, when buffered using 0.35mL of 8.4% sodium bicarbonate, the combined solutions would be approximately isotonic, which is to say that their post-combination osmolality would be approximately 300mOsm/kg.
  • a plunger could be placed 4mm proximal to the septum from the open end of a glass cartridge will be displaced approximately 4mm toward the open end of the cartridge with the addition of 0.15mL of solution.
  • the glass cartridge, or other container would be partially filled to accept the addition of a buffering solution, such as sodium bicarbonate, without over filling the glass cartridge, or other container, which may result in the plunger being disengaged from the glass cartridge.
  • a buffering solution such as sodium bicarbonate
  • One embodiment of the present invention also includes a cap, or other barrier, over the plunger end of the glass cartridge to keep sterile the area of the glass cartridge between the outward end of the plunger and the end of the glass cartridge. Without a cap, or other barrier, this area of the glass cartridge would be open to the environment and consequently may contaminate the local anesthetic solution after it is buffered with the buffering solution.
  • the barrier may be made of a substance that permeable to gas but not biologies, for instance Tyvex, and it may also be easily penetrable by the syringe's harpoon, so that the cartridge can function in the normal way intended for local anesthetic cartridges in aspirating dental syringes.
  • a hypotonic local anesthetic solution could be formulated at slightly above the standard, for instance as a 2.4% solution, so that after it is combined with 0.35mL of sodium bicarbonate buffering solution, the resulting concentration of local anesthetic solution would be close to or at the standard 2%.
  • a formula that included a greater concentration of epinephrine in the original solution would make it possible that after the buffering solution is added the epinephrine would be at its traditional concentration, for instance 1 :200,000, 1 : 100,000, or 1 :50,000.
  • a still further aspect to the invention is to create a mechanism by which the hypotonic cartridge cannot be used with a standard dental anesthetic syringe until the buffering system has completed the transfer of buffering solution into the anesthetic cartridge.
  • the crimp cap on the hypotonic local anesthetic cartridge can be fitted with a plastic clip that is too large to allow the anesthetic cartridge to be used in a traditional dental syringe or with the other standard dental anesthetic delivery devices (Comfort Control, The Wand, etc.).
  • the buffering system could include a feature that removes the clip as part of the buffering process, for instance if the cartridge connector included a flange that would disconnect the clip as the anesthetic cartridge was being inserted into the connector. In this way, if using a hypotonic solution was considered undesirable and a feature to prevent accidentally using a cartridge that had yet to be cycled through the system, for instance the Onpharmat mixing pen and Cartridge Connector, it would be more difficult to accidentally use an unbuffered hypotonic anesthetic cartridge.
  • a plug would be inserted into this "gap," and the plug would be configured such that the syringe's piston or other device that would normally push against the plunger to dispense fluid would be prevented from moving forward by the plug. After the plunger has been moved distally by the addition of the buffering solution, this plug could be easily grasped and removed.
  • This mechanism would be applicable outside the context of buffering anesthetic, to any context where a cartridge of one medical solution is intended to be used only after it has been compounded with another medical solution that is added to the first medical solution's cartridge.
  • An example of such a mechanism is shown in Figures 1-4.
  • Figure 1 shows a cartridge 1 that has been partially filled in anticipation of delivery of solution from container 7, through transfer tube 8. It is expected that as fluid transfers from container 7 into cartridge 1 , plunger 3 will be driven distally from septum 4 (to the left in this drawing), toward the open end of the glass housing 2, and it will begin to occupy space 10, which has been left for this purpose.
  • Figure 2 shows plug 11, which is intended to be inserted into space 10, as shown in figure 3, which is the configuration of the cartridge before buffering (or for other medical compounding applications, prior to admixing a second medical solution with the medical solution in the target cartridge).
  • the piston on the cartridge which normally would press the plunger 3 proximally (rightward) toward septum 4, would instead strike plug 11.
  • the piston would be prevented from moving any further proximally to septum 4, or from moving plunger 3, thus fluid could not be dispensed from the cartridge in figure 3.
  • FIG. 4 shows cartridge 1 in the configuration representative of cartridge 1 after the buffering solution (or other medical solution) has been dispensed into cartridge 1 from container 9, which has moved plunger 3 distally (leftward) from septum 4. This has displaced plug 11 , which can be grasped easily by the practitioner and removed from open space 10 in cartridge 1. Once plug 11 has been removed, cartridge 1 can be loaded into a dispensing device such as a dental syringe, which can function as normal to dispense the buffered or otherwise compounded medical solution, in the normal fashion.
  • a dispensing device such as a dental syringe
  • the invention disclosed herein limits the potential side effects of injecting hypertonic local anesthetics, while allowing the pH to be adjusted to the level deemed optimal for improving the anesthetic's performance.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Hematology (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

Les anesthésiants et autres solutions médicales sont entreposés dans une cartouche comprenant un corps creux doté d'un septum dans lequel une aiguille peut pénétrer en une extrémité et d'un piston en l'autre extrémité. Un bouchon de protection est inséré dans l'extrémité ouverte du piston de la cartouche et protège la cartouche d'une contamination suite à l'utilisation. Un tampon ou un autre matériau peut être injecté dans la cartouche, ce qui provoque le déplacement du bouchon de protection et ce qui permet alors à la cartouche d'être utilisée dans une seringue ou un autre système d'administration. L'anesthésiant peut contenir au moins un soluté et présenter une tonicité initiale et un pH initial. Un volume de tampon peut être injecté au travers du septum dans l'anesthésiant, où la concentration initiale en soluté et le pH initial de l'anesthésiant peuvent être sélectionnés en vue d'obtenir un pH cible et une tonicité cible après que le tampon a été introduit.
PCT/US2013/069300 2012-11-08 2013-11-08 Procédé et appareil destinés à ajouter des tampons et d'autres substances à des cartouches médicales WO2014074920A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2015541957A JP2015533619A (ja) 2012-11-08 2013-11-08 医療用カートリッジに緩衝剤及び他の物質を追加する方法及び装置
EP13852986.2A EP2916889A4 (fr) 2012-11-08 2013-11-08 Procédé et appareil destinés à ajouter des tampons et d'autres substances à des cartouches médicales
KR1020157015002A KR20150095651A (ko) 2012-11-08 2013-11-08 의료용 카트리지에 완충제와 다른 물질들을 첨가하기 위한 기구와 방법
AU2013342179A AU2013342179A1 (en) 2012-11-08 2013-11-08 Method and apparatus for adding buffers and other substances to medical cartridges
BR112015009466A BR112015009466A2 (pt) 2012-11-08 2013-11-08 cartucho de medicamento líquido e métodos para tamponar solução de medicamento carregada em recipiente e medicamento líquido tendo tonicidade e ph alvos
CA2888834A CA2888834A1 (fr) 2012-11-08 2013-11-08 Procede et appareil destines a ajouter des tampons et d'autres substances a des cartouches medicales
CN201380058386.5A CN104918646A (zh) 2012-11-08 2013-11-08 用于将缓冲剂和其它物质添加到医疗筒的方法和设备
MX2015005807A MX2015005807A (es) 2012-11-08 2013-11-08 Metodo y aparato para añadir reguladores de ph y otras sustancias a cartuchos medicos.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261796370P 2012-11-08 2012-11-08
US61/796,370 2012-11-08
US14/068,480 2013-10-31
US14/068,480 US20140124514A1 (en) 2012-11-08 2013-10-31 Method and apparatus for adding buffers and other substances to medical cartridges

Publications (1)

Publication Number Publication Date
WO2014074920A1 true WO2014074920A1 (fr) 2014-05-15

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ID=50621422

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/069300 WO2014074920A1 (fr) 2012-11-08 2013-11-08 Procédé et appareil destinés à ajouter des tampons et d'autres substances à des cartouches médicales

Country Status (10)

Country Link
US (1) US20140124514A1 (fr)
EP (1) EP2916889A4 (fr)
JP (1) JP2015533619A (fr)
KR (1) KR20150095651A (fr)
CN (1) CN104918646A (fr)
AU (1) AU2013342179A1 (fr)
BR (1) BR112015009466A2 (fr)
CA (1) CA2888834A1 (fr)
MX (1) MX2015005807A (fr)
WO (1) WO2014074920A1 (fr)

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US20140224376A1 (en) * 2013-02-14 2014-08-14 Onpharma, Inc. Methods and systems for buffering solutions with controlled tonicity
SG11202004467PA (en) * 2017-11-17 2020-06-29 Swedish Orphan Biovitrum Ab Publ Syringe assembly with ion-exchange material
US11083845B2 (en) * 2017-12-20 2021-08-10 Device And Apparatus Llc Apparatus and method for neutralizing local anesthetic
US11484112B2 (en) * 2018-11-13 2022-11-01 Colgate-Palmolive Company Method of whitening teeth
US10307336B1 (en) 2018-12-17 2019-06-04 John C. Sands System and method for mixing and delivering a solution

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US20050113747A1 (en) * 2002-04-24 2005-05-26 Andrew Moir Device for preparing a medicinal liquid and method for preserving a solution of medicament for injection
US6948522B2 (en) * 2003-06-06 2005-09-27 Baxter International Inc. Reconstitution device and method of use
US20120034307A1 (en) * 2006-07-24 2012-02-09 Akorn, Inc. Aqueous gel formulation and method for inducing topical anesthesia
US8162917B2 (en) * 2008-05-21 2012-04-24 Onpharma, Inc. Methods and apparatus for buffering anesthetics
US20110247722A1 (en) * 2010-04-07 2011-10-13 Onpharma, Inc. Method and systems for buffering anesthetic cartridges with buffering solutions

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Also Published As

Publication number Publication date
KR20150095651A (ko) 2015-08-21
BR112015009466A2 (pt) 2017-07-04
EP2916889A4 (fr) 2016-06-29
CN104918646A (zh) 2015-09-16
AU2013342179A1 (en) 2015-05-07
JP2015533619A (ja) 2015-11-26
US20140124514A1 (en) 2014-05-08
MX2015005807A (es) 2016-03-11
EP2916889A1 (fr) 2015-09-16
CA2888834A1 (fr) 2014-05-15

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